Mitochondrial DNA Copy Number as a Predictor of Cardiovascular Disease

Mitochondrial dysfunction is a core component of cardiovascular disease (CVD) and is associated with several CVD risk factors (diabetes, cigarette smoke exposure, and hypertension). We therefore explored the association of mitochondrial DNA copy number, which reflects oxidative stress, with prevalent and incident CVD, and its potential utility as a novel clinical biomarker of CVD. We determined mtDNA copy number in DNA extracted from whole blood in 16,401 samples from two large multi-center prospective studies_the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study. Lower mtDNA copy number was associated with increased prevalence of CVD in 4,109 white participants from CHS (OR for lowest quintile [Q1] to highest quintile [Q5] of mtDNA copy number=2.35, 95% CI=1.74-3.19, P 7.5%) risk. While we do not see the association with incident CVD in samples from CHS, this finding may reflect underlying differences in participants’ ages between the cohorts. The mean age in CHS is 72.4 years versus 58.1 years in ARIC suggesting that the association of mtDNA copy number with incident CVD may weaken with age. Given the magnitude of the effect we observe in ARIC, and the ease and low cost of the assay, we suggest that assessment of mtDNA copy number may have clinical utility for CVD risk classification warranting further validation in additional large prospective cohorts.